Quantification and localisation of FOXP3+ T lymphocytes and relation to hepatic inflammation during chronic HCV infection.

Journal article

BACKGROUND/AIMS: T lymphocyte-mediated immune reactions are closely involved in the pathogenesis of HCV-induced chronic liver disease. Regulatory T cells are able to suppress HCV-specific T lymphocyte proliferation and cytokine secretion during chronic HCV infection. We wished to address to what extent regulatory T cells exist in the livers of HCV+ individuals, and what the role of such cells might be in disease progression. METHODS: We analysed the frequency and distribution of FOXP3+ cells, along with CD4, CD8 and CD20+ cells, in liver biopsies of 28 patients with chronic HCV and 14 patients with PBC, and correlated these data with histological parameters. RESULTS: A striking number of FOXP3+ cells were present in the portal tract infiltrates of HCV-infected livers. FOXP3+ cells were largely CD4+ and there was a remarkably consistent ratio of total CD4+:FOXP3+ cells in liver across a wide range of disease states of around 2:1. This differed substantially from the ratio observed in PBC (10:1, P=0.001). CONCLUSIONS: An unexpectedly high proportion of the cellular infiltrate in persistent HCV infection comprises FOXP3+ cells. The relative proportion of FOXP3+ cells remains similar in both mild and severe fibrosis. These cells are likely to play a critical role in intrahepatic immune regulation, although their overall role in disease progression remains to be determined.

Authors: Ward, S; Fox, B; Brown, P; Worthington, J; Fox, S

• Publication status: Published
• Journal: Journal of hepatology
• Volume: 47
• Issue: 3
• Pages: 316-324
• Publication date: 2007-09-01
• DOI: 10.1016/j.jhep.2007.03.023
• EISSN: 1600-0641
• ISSN: 0168-8278
• Language: English
• Keywords: Leukocyte Count; Middle Aged; Biopsy; Forkhead Transcription Factors; Humans; Severity of Illness Index; Liver; Liver Cirrhosis, Biliary; Male; CD8-Positive T-Lymphocytes; Female; Hepatitis C, Chronic; CD4-Positive T-Lymphocytes; Adult; Disease Progression; T-Lymphocytes, Regulatory; B-Lymphocytes